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Heat shock proteins are co-opted for cancer
Date:9/20/2007

CAMBRIDGE, Mass. (Sept. 20, 2007) A Jekyll-Hyde mechanism that both protects healthy cells and enables cancer cells could be the basis for new cancer-fighting drugs.

Scientists in the laboratory of Whitehead Member Susan Lindquist have discovered that a certain transcription factora protein that binds to specific areas of the genome and acts to switch genes on and offknown to aid in handling stresses also facilitates the survival of cancer cells.

According to the study, which appears online in Cell on Sept. 20, this transcription factor may be the basis for powerful new ways to fight cancer.

The transcription factor is the master regulator of cells protective heat-shock responsea complex and multifaceted defense system that kicks in when an organism is exposed to increased temperature, infection, toxins or other stresses. The heat-shock response is thought to have existed for more than a billion years and is found in organisms from bacteria to fruit flies to humans.

Heat-shock transcription factors turn on genes for helpful chaperone proteins that help keep proteins from going bad. If proteins form unhealthy clumps, heat-shock proteins (HSPs) pull them apart. If proteins misfold, HSPs help them refold. If the errant proteins are too far gone, HSPs ship them off to be destroyed.

Postdoctoral associate Chengkai Dai and his colleagues looked at the role of heat-shock factor 1 (HSF1), the master regulator of the heat-shock response, in enabling normal cells to turn into cancer cells.

This work provides the first direct evidence of an important role for HSF1 in helping cells to undergo a malignant transformation, says co-author Luke Whitesell, a research scientist in the Lindquist lab.

While the transcription factor does not itself cause the transformation of a normal cell into a cancer cell, it orchestrates a network of core functions in the cancer cells that govern their proliferation, survival,
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Contact: Eric Bender
bender@wi.mit.edu
617-258-9183
Whitehead Institute for Biomedical Research
Source:Eurekalert

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